Vitamin D Deficiency (VDD) and Susceptibility towards Severe Dengue Fever-A Prospective Cross-Sectional Study of Hospitalized Dengue Fever Patients from Lahore, Pakistan.

Dengue is a mosquito-borne flaviviral serious febrile illness, most common in the tropical and subtropical regions including Pakistan. Vitamin D is a strong immunomodulator affecting both the innate and adaptive immune responses and plays a pivotal role in pathogen-defense mechanisms. There has been considerable interest in the possible role of vitamin D in dengue viral (DENV) infection. In the present prospective cross-sectional study, we assessed a possible association between serum vitamin D deficiency (VDD) and susceptibility towards severe dengue fever (DF) illness. Serum vitamin D levels were measured at the time of hospitalization in 97 patients diagnosed with dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) at Mayo Hospital, King Edward Medical University, Lahore, PK, from 16 November 2021 to 15 January 2022. In terms of disease severity, 37 (38.1%) patients were DF, 52 (53.6%) were DHF grade 1 and 2, and 8 (8.2%) were DSS. The results revealed that most patients (75 (77.3%)) were vitamin-D-deficient (i.e., serum level < 20 ng/mL), including 27 (73.0%) in DF, 41 (78.8%) in DHF grade 1 and 2, and 7 (87.5%) in DSS. The degree of VDD was somewhat higher in DSS patients as compared to DF and DHF grade 1 and 2 patients. Overall, serum vitamin D levels ranged from 4.2 to 109.7 ng/mL, and the median (IQR) was in the VDD range, i.e., 12.2 (9.1, 17.8) ng/mL. Our results suggest that there may be a possible association between VDD and susceptibility towards severe dengue illness. Hence, maintaining sufficient vitamin D levels in the body either through diet or supplementation may help provide adequate immune protection against severe dengue fever illness. Further research is warranted.

Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study.

Anatomical and physiological considerations indicate that the oral cavity is a primary source of the lung microbiota community, and recent studies have shown that the microbiota in the lungs contributes to immunological homeostasis, potentially altering the organ's susceptibility to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection, lung Gram-negative bacteria could promote the cytokine cascade with a better performance than a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To verify if the modulation of the oral microbiota could have an impact on the current coronavirus disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled trial seem to prove the potential role of this oral strain in improving the course of the main markers of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic structure could modulate the inflammatory processes generated at the pulmonary and systemic level by a viral infection.

Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial.

Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported. Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05130671.

Unnecessary Use of Corticosteroids for managing early mild symptoms of COVID-19 may lead to Rhino-ortibal-cerebral mucormycosis in Patients with Diabetes - a case series from Lahore, Pakistan.

Rhino-orbital-cerebral mucormycosis (ROCM), a rare but fatal fungal infection, has recently emerged as a serious complication after corticosteroids therapy in COVID-19 patients, predominantly in diabetic and immunocompromised patients. The World Health Organization (WHO) COVID-19 current guidelines recommend corticosteroids administration in hospitalized COVID-19 patients requiring supplementary oxygen or mechanical ventilation. Herein, we report a case series of seven patients with COVID-19; three mild, three moderate, and one severe, from Lahore, Pakistan; all were using corticosteroids for managing their early mild symptoms of COVID-19 at home for around 2-3 weeks without a physician's advise, presented, and admitted with ROCM to Mayo hospital, Lahore, from March to June 2021. Out of the seven patients, five patients had uncontrolled diabetes mellitus (DM) as comorbidity. Eye pain, facial swelling and pain, nasal blockage, and black coloration around eyes, on palate, and oral mucosa were the presenting complaints at the time of admission. All the patients had radiographic imaging, including computed tomography (CT), paranasal sinuses (PNS), or brain magnetic resonance imaging (MRI) carried out at the hospital, which confirmed mucosal thickening and adjacent sinus bony erosions with intracranial extension. All the patients were treated with local debridement of the infected necrotic tissue along with intravenous liposomal Amphotericin B and Posaconazole or Amphotericin B depending on the case. Due to timely management, in six out of seven patients, prognosis was good due to early diagnosis and treatment, while one patient with severe COVID-19 illness deteriorated and died. The misuse of corticosteroids for managing early mild symptoms of COVID-19 in diabetic and other immunocompromised patients can lead to fatal ROCM, which can further increase their risk of developing severe COVID-19 and mortality. It is stressed that only physician's recommended therapeutic advice should be followed for managing early mild symptoms of COVID-19 in self-isolation and avoid the unnecessary use of corticosteroids. This case series also emphasizes that COVID-19 diabetic patients treated with corticosteroids need more vigilant monitoring and high suspicion of early diagnosis and treatment of invasive fungal infection. Early diagnosis and management can reduce morbidity and mortality.

Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial.

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host's hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04861298.

Papillon-Lèfevre syndrome with palmoplantar keratoderma and periodontitis, a rare cause of pyrexia of unknown origin: a case report.

INTRODUCTION: Papillon-Lefèvre Syndrome is a rare autosomal recessive disorder characterized by diffuse, transgradient palmoplantar keratoderma, destructive periodontitis beginning in childhood, premature loss of primary teeth, and frequent cutaneous and systemic pyogenic infections. Pyogenic liver abscess is an uncommon presentation of the disease present in this case. CASE PRESENTATION: A 16-year-old Punjabi, Pakistani boy presented to the outpatient department of a tertiary-care hospital of Lahore with high-grade fever of 2 months duration. He had been treated for a pyogenic liver abscess 2 years back with antibiotics followed by incision and drainage. He had poor orodental hygiene, palmoplantar keratoderma and periodontitis. His parents had history of consanguinity. His brother and two cousins had similar skin lesions and were edentulous. An orthopentogram showed atrophy of the alveolar bone. He was treated with broad-spectrum antibiotics, and antipyretics for systemic infection. Multivitamins, topical steroids, topical keratolytics and emollients were used for his dermatological issues. CONCLUSIONS: Our patient was successfully treated. His fever settled and his skin lesions improved with antibiotics, topical steroids and keratolytics. He was sent home and was asked to return for follow-up on a monthly basis.